Systematic review on intentional non-medical fentanyl use among people who use drugs.

Objectives: Fentanyl is a highly potent opioid and has, until recently, been considered an unwanted contaminant in the street drug supply among people who use drugs (PWUD). However, it has become a drug of choice for an increasing number of individuals. This systematic review evaluated intentional non-medical fentanyl use among PWUD, specifically by summarizing demographic variance, reasons for use, and resulting patterns of use. Methods: The search strategy was developed with a combination of free text keywords and MeSH and non-MeSH keywords, and adapted with database-specific filters to Ovid MEDLINE, Embase, Web of Science, and PsychINFO. Studies included were human studies with intentional use of non-medical fentanyl or analogues in individuals older than 13. Only peer-reviewed original articles available in English were included. Results: The search resulted in 4437 studies after de-duplication, of which 132 were selected for full-text review. Out of 41 papers included, it was found that individuals who use fentanyl intentionally were more likely to be young, male, and White. They were also more likely to have experienced overdoses, and report injection drug use. There is evidence that fentanyl seeking behaviours are motivated by greater potency, delay of withdrawal, lower cost, and greater availability. Conclusions: Among PWUD, individuals who intentionally use fentanyl have severe substance use patterns, precarious living situations, and extensive overdose history. In response to the increasing number of individuals who use fentanyl, alternative treatment approaches need to be developed for more effective management of withdrawal and opioid use disorder. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42021272111.

Opioid agonist treatment in transition: A cross-country comparison between Austria, Germany and Switzerland.

BACKGROUND AND AIMS: OAT is a well developed and successful treatment strategy for opioid dependent patients in Europe. It has significantly contributed to the fight against the HIV and HCV pandemics, leading to an increased life expectancy in this population. Building on the OAT experiences in Austria, Germany, and Switzerland and their models of care, the objective of this study is to analyse experiences and changes in patient structures to identify necessary adaptations for the system of care. METHODS: We analysed national register-based data from patients receiving OAT during the period spanning from 2010 to 2020 in Austria, Germany (cases), and Switzerland. We examined and compared OAT policies and practice at national levels through a review of literature and publicly available policy documents. RESULTS: Across these three countries, the life expectancy of OAT patients increased substantially. The mean age increased from 33.0 in 2010 to 39.1 in 2020 in Austria, from 35.6 years to 41.5 years in Germany (cases), and from 39.6 to 47.1 in Switzerland, respectively. In all three countries, the percentage of patients/cases aged 60 years and older increased more than tenfold between 2010 and 2020. CONCLUSIONS: Integrated support models, reliable care structures, internationally comparable high treatment coverage, flexible prescribing practices, and a wide range of available OAT medications are successful strategies. The experiences in these countries indicate that it is possible to address the complex and chronic nature of opioid dependence and its concurrent mental and physical health challenges, resulting in an increasing life expectancy of OAT patients.

Patterns of anxiety, depression, and substance use risk behaviors among university students in Canada.

Objective: To identify subgroups of students with distinct profiles of mental health symptoms (MH) and substance use risk (SU) and the extent to which MH history and socio-demographics predict subgroup membership. Participants: University students (N = 10,935: 63% female). Methods: Repeated cross-sectional survey administered weekly to stratified random samples. Latent class analysis (LCA) was used to identify subgroups and multinomial regression was used to examine associations with variables of interest. Results: LCA identified an optimal 4-latent class solution: High MH-Low SU (47%), Low MH-Low SU (22%), High MH-High SU (19%), and Low MH-High SU (12%). MH history, gender, and ethnicity were associated with membership in the classes with high risk of MH, SU, or both. Conclusion: A substantial proportion of students presented with MH, SU, or both. Gender, ethnicity and MH history is associated with specific patterns of MH and SU, offering potentially useful information to tailor early interventions.

Shifting drug markets in North America - a global crisis in the making?

Understanding drug market dynamics and their underlying driving factors is paramount to developing effective responses to the overdose crisis in North America. This paper summarises the distinct drug market trends observed locally and internationally over the past decade to extrapolate future drug market trajectories. The emergence of fentanyl on North American street markets from 2014 onwards led to a shift of street drug use patterns. Previously perceived as contaminants, novel synthetic opioids became the drugs of choice and a trend towards higher potency was observed across various substance classes. The diversification of distribution strategies as well as the regionalisation and industrialisation of production followed basic economic principles that were heavily influenced by prosecution and policy makers. Particularly, the trend towards higher potency is likely most indicative of what to expect from future illicit drug market developments. Nitazenes and fentanyl-analogues, several times more potent than fentanyl itself, are increasingly detected in toxicological testing and have the potential of becoming the drugs of choice in the future. The dynamic of drug import and local production is less clear and influenced by a multitude of factors like precursor availability, know-how, infrastructure, and the success of local drug enforcement strategies. Drug market dynamics and the current trajectory towards ultrapotent opioids need to be recognised by legislation, enforcement, and the health care system to prepare effective responses. Without significant improvements in treatment access, the implementation of preventative approaches and early warning systems, the mortality rate will continue to increase. Furthermore, there is no mechanism in place preventing the currently North American focused overdose crisis to spread to other parts of the globe, particularly Europe. A system of oversight, research, and treatment is needed to address mortality rates of historic proportions and prevent further harm.

The Fentanyl System Shock - Are There Lessons to Learn From the COVID-19 System Shock Framework? Comment on "The COVID-19 System Shock Framework: Capturing Health System Innovation During the COVID-19 Pandemic".

The Sydney Children's Hospitals Network (SCHN) addressed the challenges of the COVID-19 pandemic by implementing innovative changes which made their health system resilient and responsive. For other healthcare systems, there are important takeaways. In the United States and Canada, an urgent widespread response is needed to address the overdose crisis, driven by potent synthetic opioids (ie, fentanyl and its derivates). We project the COVID-19 System Shock Framework (CSSF) on to the North American healthcare systems and suggest a Fentanyl System Shock Framework, which provides a framework for necessary changes and innovations to address the overdose crisis. To become resilient to the fentanyl system shock, core components as well as overarching values, health policy, and online technologies need to be adapted to reduce the death count and meet the evolving needs of marginalised individuals who use opioid. Future research should focus on scientifically assessing such implementations to guide evidence-based decision making.

Sexual dysfunction prevalence, risk factors, and help-seeking behavior in opioid agonist treatment and general psychiatry: a cross-sectional study.

Background: Mental disorders pose a high risk for the occurrence of sexual dysfunctions (SD). This study aimed to investigate prevalence of risk factors and help-seeking behavior for sexual dysfunctions in patients with opioid use disorder compared to patients seeking psychotherapeutic help. Methods: Ninety-seven patients at two opioid agonist treatment (OAT) centers and 65 psychotherapeutic patients from a psychiatric practice (PP) in Switzerland were included in the study. Self-report assessments comprised sexual functioning (IIEF: International Index of Erectile Function; FSFI: Female Sexual Function Index), depressive state, psychological distress, alcohol consumption, nicotine use, and a self-designed questionnaire on help-seeking behavior. We used chi-squared and Mann-Whitney U tests for group comparisons and binary logistic regression models to identify variables predicting the occurrence of sexual dysfunctions. Results: There was no statistically significant difference (p = 0.140) in the prevalence of SD between OAT (n = 64, 66.0%) and PP sample (n = 35, 53.8%). OAT patients scored significantly higher in scales assessing nicotine use (p < 0.001) and depressive state (p = 0.005). Male OAT patients scored significantly worse on the Erectile Function scale (p = 0.005) and female PP patients scored significantly worse on the FSFI Pain domain (p = 0.022). Opioid use disorder, higher age, and being female predicted the occurrence of SD in the total sample. In the OAT sample, only higher age remained predictive for the occurrence of SD. A lack of help-seeking behavior was observed in both groups, with only 31% of OAT patients and 35% of PP patients ever having talked about their sexual health with their treating physician. Conclusion: SD are common among psychiatric patients receiving OAT and general psychiatric patients seeking psychotherapy. Professionals providing mental healthcare to patients must emphasize prevention and routine assessments of sexual functioning needs.

Benzodiazepine use, quality of life and psychiatric symptom burden in oral and injectable opioid agonist treatment: a cross-sectional study.

BACKGROUND: Use of benzodiazepines (BZD) in patients receiving opioid agonist treatment (OAT) is common and associated with a variety of negative health and social outcomes. This cross-sectional study investigates the impact of BZD use in OAT patients on their quality of life (QoL). METHODS: A convenience sample of patients receiving oral OAT or heroin-assisted treatment in two outpatient centres in Basel, Switzerland was investigated. Participants (n = 141) completed self-report questionnaires on psychiatric symptoms and psychological distress (The Symptom Checklist 27, SCL-27), depressive state (German version of the Center for Epidemiological Studies Depression Scale), quality of life (Lancashire Quality of Life Profile, LQOLP) and use of BZD and other drugs (self-report questionnaire). Substance use was assessed by urine toxicology testing. RESULTS: In bivariate analysis, total QoL scores were significantly lower for lifetime, current, and prolonged BZD users compared to participants without the respective use patterns. There was no significant relationship between BZD dose and QoL. In multivariable linear regression models controlling for psychiatric symptom load and depressive state, only lifetime use predicted lower QoL, whereas other BZD use patterns were not significantly associated. CONCLUSIONS: The association of lower QoL and BZD use in OAT patients is strongly confounded by co-occurring depressive state and psychiatric symptoms. Careful diagnosis and treatment of co-occurring mental disorders in OAT is paramount to improve QoL in this patient population and may also help reduce BZD use.

Feasibility, safety, and acceptability of intranasal heroin-assisted treatment in Switzerland: protocol for a prospective multicentre observational cohort study.

BACKGROUND: Heroin-assisted treatment (HAT) is a proven effective treatment option for individuals with severe opioid use disorder (OUD). In Switzerland, pharmaceutical heroin (diacetylmorphine, DAM) is available in tablet form or as injectable liquid. This creates a large barrier for individuals who require the rapid onset of effect but are either unable or do not want to inject, or who primarily snort opioids. Early experimental data has demonstrated that intranasal DAM administration can be a viable alternative to the intravenous or intramuscular route of administration. The purpose of this study is to assess the feasibility, safety, and acceptability of intranasal HAT. METHODS: This study will assess intranasal DAM using a prospective multicentre observational cohort study design in HAT clinics across Switzerland. Patients will be offered to switch from oral or injectable DAM to intranasal DAM. Participants will be followed-up over 3 years, with assessments at baseline, and after 4, 52, 104 and 156 weeks. The primary outcome measure (POM) is retention in treatment. Secondary outcomes (SOM) include prescriptions and routes of administration of other opioid agonists, illicit substance use, risk behaviour, delinquency, health and social functioning, treatment adherence, opioid craving, satisfaction, subjective effects, quality of life, physical health, and mental health. CONCLUSIONS: The results derived from this study will generate the first major body of clinical evidence on the safety, acceptability, and feasibility of intranasal HAT. If proven to be safe, feasible and acceptable, this study would increase the accessibility of intranasal OAT for individuals with OUD globally as a critical improvement in risk reduction.

Safety and feasibility of intranasal heroin-assisted treatment: 4-week preliminary findings from a Swiss multicentre observational study.

BACKGROUND: Heroin-assisted treatment (HAT) is effective for individuals with severe opioid use disorder (OUD) who do not respond sufficiently to other opioid agonist treatments. It is mostly offered with injectable diacetylmorphine (DAM) or DAM tablets creating a barrier for individuals who need the rapid onset of action but are either unable or unwilling to inject, or primarily snort opioids. To explore another route of administration, we evaluated the safety and feasibility of intranasal (IN) DAM. METHODS: This is a multicentre observational cohort study among patients in Swiss HAT. All patients planning to receive IN DAM within the treatment centres were eligible to participate. Participants were either completely switched to IN DAM or received IN DAM in addition to other DAM formulations or opioid agonists. Patients were followed up for four weeks. Sociodemographic characteristics, current HAT regimen, reasons for starting IN DAM, IN DAM doses, number of injection events in the sample, IN DAM continuation rate, and appearance of adverse events and nose-related problems were evaluated. RESULTS: Participants (n = 52) reported vein damage, preference for nasal route of administration, and desire of a stronger effect or for a less harmful route of administration as primary reasons for switching to IN DAM. After four weeks, 90.4% of participants (n = 47) still received IN DAM. Weekly average realised injection events decreased by 44.4% from the month before IN DAM initiation to the month following. No severe adverse events were reported. CONCLUSIONS: After four weeks, IN DAM was a feasible and safe alternative to other routes of administration for patients with severe OUD in HAT. It addressed the needs of individuals with OUD and reduced injection behaviour. More long-term research efforts are needed to systematically assess efficacy of and patient satisfaction with IN DAM.

Developing A Rapid Transfer from Opioid Full Agonist to Buprenorphine: "Ultrarapid Micro-Dosing" Proof of Concept.

Buprenorphine/naloxone has been shown to be effective for treating opioid use disorder (OUD). However, the traditional method of induction requires a patient to be in moderate-to-severe withdrawal, which is challenging, time-consuming, and a common reason for leaving against medical advice. Induction strategies that minimize the severity and duration of patient discomfort while enabling patients to reach therapeutic doses during short hospital admissions can mitigate difficulties when inducing a patient on buprenorphine/naloxone. This case-series illustrates two patients with OUD using illicit fentanyl, who were successfully started on buprenorphine/naloxone using 24-hour and 6-hour micro-dosing induction protocol. During induction, the patients were up-titrated to a therapeutic dose through ultrarapid micro-dosing with ongoing use of short-acting opioids. Both patients reached therapeutic doses experiencing minimal levels of withdrawal. This case-series is a proof of concept for the use of a buprenorphine/naloxone ultrarapid micro-induction protocol for inpatients with OUD. By reducing the length of induction and precluding the need for withdrawal, this method offers several advantages over previously published inductions protocols and can improve the accessibility of buprenorphine/naloxone to patients with OUD.

Effectiveness and cost-effectiveness of sector-independent treatment coordination for people with substance-related disorders following an online assessment (ASSIST): study protocol for a randomized controlled trial.

BACKGROUND: The implementation of person-centred, need-oriented and flexible care for people with substance-related problems is often insufficient, in large part due to the complexity of addiction support services among different providers. A standardized online assessment and subsequent sector-independent treatment coordination could provide individuals with more appropriate services, thereby making better use of individual services and leading to a more effective addiction support system as a whole. The aim of this study is to determine the effectiveness and cost-effectiveness of sector-independent treatment coordination following an online assessment, in comparison with the current standard of care and treatment process in Germany. METHODS: The sample size of this randomized, controlled trial has been set to a total of 400 participants with substance-related problems. Participants living in Stuttgart, Germany, will be randomly allocated to (1) the intervention group with immediate online assessment and subsequent sector-independent treatment coordination (ASSIST) or (2) the waitlist group. Participants in the waitlist group will initially remain in usual care and only be provided with the online assessment 6 months later. Short-term effects (over 2 months) and medium-term effects (over 6 months) of ASSIST will be compared between the intervention and the waitlist groups. The primary outcome is improved treatment satisfaction. Secondary outcomes include improved subjective quality of life and empowerment, reductions in patients' substance use, unmet needs and illness-related clinical and social impairment. Health economic evaluation as well as quantitative and qualitative process evaluations will be conducted. DISCUSSION: The results of this study are expected to provide information on whether sector-independent treatment coordination following an online assessment contributes to improved health care service provision for people with substance-related problems. This randomized controlled trial will help identify facilitators and barriers to the sustainable implementation of a cross-sectoral care concept in substance abuse services. TRIAL REGISTRATION: German Clinical Trial Register DRKS00026996 . Registered on 29 October 2021.

Nasal administration of diacetylmorphine improved the adherence in a patient receiving heroin-assisted treatment.

BACKGROUND: Traditional heroin-assisted treatment in Switzerland consists of oral and injectable diacetylmorphine (pharmaceutical heroin) administration. To date, no suitable treatment option is available for patients who crave rapid onset ("rush") but are either unable to inject or primarily sniff or inhale illicit heroin. We present a patient who successfully switched to intranasal heroin-assisted treatment following several unsuccessful treatment attempts. CASE PRESENTATION: A 29-year-old male with severe opioid use disorder, injection substance use, and concomitant cocaine use, previously prescribed slow-release oral morphine, was started on intravenous diacetylmorphine. Due to complications and harms associated with intravenous injections, nasal diacetylmorphine was prescribed. With this novel route of administration, the patient who had previously been unable to adhere to other OAT options remained in treatment. Health outcomes improved by reduction of injection-related harms, increased adherence to the heroin-assisted treatment regimen, and increased collaboration with the therapeutic staff. CONCLUSIONS: Nasal heroin-assisted treatment can be a feasible therapeutic option for individuals with severe opioid use disorder who crave the fast onset of effect of diacetylmorphine but are unable to inject intravenously.

Towards an International Consensus on the Prevention, Treatment, and Management of High-Risk Substance Use and Overdose among Youth.

Background and Objectives: Now more than ever, there is an obvious need to reduce the overall burden of disease and risk of premature mortality that are associated with mental health and substance use disorders among young people. However, the current state of research and evidence-based clinical care for high-risk substance use among youth is fragmented and scarce. The objective of the study is to establish consensus for the prevention, treatment, and management of high-risk substance use and overdose among youth (10 to 24 years old). Materials and Methods: A modified Delphi technique was used based on the combination of scientific evidence and clinical experience of a group of 31 experts representing 10 countries. A semi-structured questionnaire with five domains (clinical risks, target populations, intervention goals, intervention strategies, and settings/expertise) was shared with the panelists. Based on their responses, statements were developed, which were subsequently revised and finalized through three iterations of feedback. Results: Among the five major domains, 60 statements reached consensus. Importantly, experts agreed that screening in primary care and other clinical settings is recommended for all youth, and that the objectives of treating youth with high-risk substance use are to reduce harm and mortality while promoting resilience and healthy development. For all substance use disorders, evidence-based interventions should be available and should be used according to the needs and preferences of the patient. Involuntary admission was the only topic that did not reach consensus, mainly due to its ethical implications and resulting lack of comparable evidence. Conclusions: High-risk substance use and overdoses among youth have become a major challenge. The system's response has been insufficient and needs substantial change. Internationally devised consensus statements provide a first step in system improvement and reform.

Case report: acute care management of severe opioid withdrawal with IV fentanyl.

BACKGROUND: An increasing number of individuals who use drugs in North America are preferentially consuming fentanyl over other opioids. This has significant consequences on the treatment and management of opioid use disorder (OUD) and its concurrent disorders, especially in acute care if opioid requirements are not met. CASE PRESENTATION: We present a patient with severe OUD and daily injection of fentanyl, admitted to hospital for management of acute physical health issues. Due to high opioid requirements and history of patient-initiated discharge, intravenous fentanyl was administered for treatment of opioid withdrawal, and management of pain, which supported continued hospitalization for acute care treatment and aligned with substance use treatment goals. CONCLUSION: This case demonstrates that intravenous fentanyl for management of OUD in hospital can be a feasible approach to meet opioid requirements and avoid fentanyl withdrawal among patients with severe OUD and daily fentanyl use, thereby promoting adherence to medical treatment and reducing the risk of patient-initiated discharge. There is an urgent need to tailor current treatment strategies for individuals who primarily use fentanyl. Carefully designed research is needed to further explore the use of IV fentanyl for acute care management of severe opioid withdrawal in a hospital setting.

Egyptian Students Open to Digital Mental Health Care: Cross-Sectional Survey.

BACKGROUND: In Egypt, the shortage of mental health services, particularly for adolescents and young adults, is apparent. Electronic mental health (EMH) has been proposed as a solution to bridge the gap and better address the needs of young people. However, EMH is new to Egypt and its acceptability among target populations is crucial to its implementation and success. OBJECTIVE: The objective of this study is to explore the interest of Egyptian youth in EMH, identify perceived barriers to EMH, and inform the design of EMH tools to best address the needs of youth. METHODS: A web-based cross-sectional survey was distributed among medical students at Tanta University in Egypt. Chi-square and one-way analysis of variance tests were performed for inferential analyses using a significance level of .05. RESULTS: Of the 707 individuals who completed the survey (90.9% response rate), 60.5% (428) were female, 62% (438) lived in urban and suburban areas, and the mean age of the sample was 20.5 (SD 1.8) years. The vast majority of participants (522/707, 73.8%) had already used the internet to find information about mental health problems, but the information was unsatisfactory for about half of them (386/707, 54.6%). Almost all students reported that they would prefer web-based therapy if EMH were available through a trustworthy national web-based platform for youth mental health (601/707, 85%). Students believed that emotional difficulties, social support, and coping strategies were the main topics that EMH should help with. The most common perceived barriers for EMH use in Egypt were concerns about privacy (382/707, 54%) and a lack of technology literacy and unfamiliarity with EMH (352/707, 50%). CONCLUSIONS: EMH is a promising strategy for addressing gaps in the mental health care for young people. To construct and implement a digital system of care that addresses the unique needs and preferences of youth, adolescents and young adults should be involved in the co-development and design.

Substance of choice, impact of heroin or opium on treatment retention in a multicentre randomised controlled trial in Iran.

INTRODUCTION: In the Middle East and Asia, illicit opioid use exists across a spectrum between heroin and opium. The impact of primary opioid of choice on opioid agonist treatment retention has not been well evaluated previously, especially for opium tincture, an increasingly popular form of opioid agonist treatment in Iran. This study investigates the relationship between primary opioid of choice, namely heroin or opium, and retention in opium tincture and methadone treatment. METHODS: Participants with opioid use disorder (n = 204) were randomised to receive opium tincture or methadone. All participants were categorised as mainly using opium or heroin. Bivariate analyses between treatment retention and primary opioid of choice (P < 0.05) and logistic regression were conducted. RESULTS: Among the 191 participants included in this analysis, heroin was the primary substance of choice for 135 participants (70.7%) and opium for 56 (29.3%). Bivariate analysis showed that the opium group was more likely to be satisfied with family situation, employed and retained in treatment than the heroin group while less likely to experience incarceration and use multiple substances. When adjusting for covariates, primary opioid of choice was not significantly associated with retention in either methadone or opium tincture treatment arm. DISCUSSION AND CONCLUSIONS: Positive factors, such as employment, housing and family support, seem to collectively explain the higher retention in treatment among those who primarily use opium compared to those who use heroin. To optimise retention in opioid agonist treatment, biopsychosocial care models should be further evaluated to improve psychosocial functioning.

Mental health outcomes and help-seeking behaviours among Egyptian medical students: A cross-sectional study.

AIM: Approximately half of the population in Egypt is under the age of 25. Globally, mental illness represents the highest burden of disease in this age group. Yet in Egypt, there is still no youth-specific mental health system in place and the vast majority of young people do not have access to any professional mental health support. The objective of this study was to describe the mental health needs of Egyptian youth and the resources they use when seeking help. METHODS: An online cross-sectional survey was distributed among medical students at Tanta University in Egypt. Of the 707 individuals who completed the survey (90.9% response rate), 60.5% were female, 62.0% lived in urban and suburban areas, and the mean age of the sample was 20.5 (±1.8) years old. RESULTS: More than half (54%) of the students reported that they had been affected by mental health problems at some point in their lives. Anxiety and depression were the most common problems. Regarding help-seeking behaviours, participants mainly searched the web or spoke to peers and relatives; few reported approaching medical professionals. The majority of participants (59.7%) reported being disappointed with the current mental health care system in Egypt. CONCLUSIONS: There is a high prevalence of mental challenges among Egyptian youth and the health care system is not adequately prepared to respond to their needs. E-Mental Health and online interventions seem to be a promising solution that could increase access to mental health services for Egyptian youth.